2,4,6-Trichlorobenzoyl chloride → N-(1-((1,5-dimethyl-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79376

Reaction equation

HRID 79376 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]3[C:17]([C:20]([O-:22])=O)=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH2:4][CH2:3]1.[Li+].ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH3:36][N:37]1[C:41]([CH3:42])=[CH:40][C:39]([CH2:43][N:44]2[C:52]3[CH:51]=[CH:50][CH:49]=[C:48]([NH2:53])[C:47]=3[C:46]([CH2:54][CH3:55])=[N:45]2)=[N:38]1>CN1C(=O)CCC1.[OH-].[Na+].CCOC(C)=O>[CH3:36][N:37]1[C:41]([CH3:42])=[CH:40][C:39]([CH2:43][N:44]2[C:52]3[C:47](=[C:48]([NH:53][C:20]([C:17]4[N:14]5[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:5]6[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]6)=[CH:12][C:13]5=[N:19][CH:18]=4)=[O:22])[CH:49]=[CH:50][CH:51]=3)[C:46]([CH2:54][CH3:55])=[N:45]2)=[N:38]1

Participants

7

Reactant 3

HCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 67252742Lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylateHCID 672600441-((1,5-dimethyl-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-amine

Product 1

HCID 67261556N-(1-((1,5-dimethyl-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamideYield 68.7%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
87 °C

Procedure

To a solution of lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (89.1 mg, 0.278 mmol) in NMP (6 mL) at 0° C. was added 2,4,6-trichlorobenzoyl chloride (43.5 μL, 0.278 mmol). The reaction mixture was stirred for 30 minutes. 1-((1,5-Dimethyl-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-amine (50 mg, 0.186 mmol) was added and the mixture was heated at 87° C. for 3 hours. The reaction mixture was cooled to ambient temperature, and diluted with 10% NaOH aqueous solution (5 mL) and EtOAc (20 mL). The organic phase was washed with water and brine and then concentrated under reduced pressure. The residue was triturated with Et2O to give final product (71 mg). MS (ES+APCI) m/z=556 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washThe organic phase was washed with water and brine
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-bd91e1da63934e00a5e45de0438dd907
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Linked notes

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